1. Field of the Invention
The invention relates to stents and bioactive compositions for ameliorating a vascular diseased state, particularly for the treatment of stenosis or restenosis following a vascular trauma or disease.
2. Description of the Background
Percutaneous transluminal intervention (PTI) is widely used as the primary treatment modality in many patients with coronary artery disease. PTI can relieve myocardial ischemia in patients with coronary artery disease by reducing lumen obstruction and improving coronary flow. Recurrent stenosis or restenosis, characterized by the reocclusion of the coronary arteries following PTI, remains a significant problem, however. Occurrence of immediate occlusion or development of restenosis within 6 months after the procedure, results in significant morbidity and mortality or frequently necessitates further interventions such as repeat angioplasty or coronary bypass surgery.
The processes responsible for restenosis after PTI are caused by complex interplay among several different biological agents and pathways. It has been theorized that the etiology of the disease process includes: (1) a shift in smooth muscle phenotype from a quiescent, contractile state to a migrating, proliferative form; (2) migration of the transformed smooth muscle cell from the media to the intima; and (3) massive proliferation of smooth muscle cells in the intima. Investigations of the pathogenesis of intima thickening have produced a theory that, following arterial injury, platelets, endothelial cells, macrophages and smooth muscle cells release various cytokines such as interleukin-1 (1L-1) and paracrine and autocrine growth factors such as platelet derived growth factor, epidermal growth factor, insulin-like growth factor, and fibroblast growth factor. T-cells and macrophages also migrate into the neointima. This cascade of events, as it has been suggested, results in an excessive proliferation and migration of smooth muscle cells, which causes the narrowing of the blood vessel and the reduction of the flow of blood through the vessel.
No surgical intervention or post-surgical treatment, to date, has proven significantly effective in preventing restenosis. Treatment strategies have included repeat balloon remodeling or implantation of stents. Stents are scaffoldings, usually cylindrical or tubular in shape, which function to physically hold open and, if desired, to expand the wall of the passageway. Typically stents are capable of being compressed, so that they can be inserted through small cavities via catheters, and then expanded to a larger diameter once they are at the desired location. Mechanical intervention via stents, although a significant innovation in the treatment of occlusive regions, has not reduced the development of restenosis.
Pharmaceutical agents have also been locally and systemically administered, concurrent with or following PTI, in an attempt to inhibit smooth muscle cell hyper-proliferation. The pharmaceutical agents employed in an attempt to treat restenosis have shown some favorable result. However, there is a great need for better and more effective compounds, and methods of using the compounds for the effective management of restenosis.